| Structural highlights
Function
[REV1_HUMAN] Deoxycytidyl transferase involved in DNA repair. Transfers a dCMP residue from dCTP to the 3'-end of a DNA primer in a template-dependent reaction. May assist in the first step in the bypass of abasic lesions by the insertion of a nucleotide opposite the lesion. Required for normal induction of mutations by physical and chemical agents.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
Rev1 is a translesion synthesis (TLS) DNA polymerase essential for DNA damage tolerance in eukaryotes. In the process of TLS stalled high-fidelity replicative DNA polymerases are temporarily replaced by specialized TLS enzymes that can bypass sites of DNA damage (lesions), thus allowing replication to continue or postreplicational gaps to be filled. Despite its limited catalytic activity, human Rev1 plays a key role in TLS by serving as a scaffold that provides an access of Y-family TLS polymerases poleta, iota, and kappa to their cognate DNA lesions and facilitates their subsequent exchange to polzeta that extends the distorted DNA primer-template. Rev1 interaction with the other major human TLS polymerases, poleta, iota, kappa and the regulatory subunit Rev7 of polzeta, is mediated by Rev1 C-terminal domain (Rev1-CT). We used NMR spectroscopy to determine the spatial structure of the Rev1-CT domain (residues 1157-1251) and its complex with Rev1 interacting region (RIR) from poleta (residues 524-539). The domain forms a four-helix bundle with a well-structured N-terminal beta-hairpin docking against helices 1 and 2, creating a binding pocket for the two conserved Phe residues of the RIR motif that upon binding folds into an alpha-helix. NMR spin-relaxation and NMR relaxation dispersion measurements suggest that free Rev1-CT and Rev1-CT/poleta-RIR complex exhibit mus-ms conformational dynamics encompassing the RIR binding site, which might facilitate selection of the molecular configuration optimal for binding. These results offer new insights into the control of TLS in human cells by providing a structural basis for understanding the recognition of the Rev1-CT by Y-family DNA polymerases.
NMR Structure and Dynamics of the C-terminal Domain from Human Rev1 and its Complex with Rev1 Interacting Region of DNA Polymerase eta,Pozhidaeva A, Pustovalova Y, D'Souza S, Bezsonova I, Walker GC, Korzhnev DM Biochemistry. 2012 Jun 13. PMID:22691049[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Lin W, Xin H, Zhang Y, Wu X, Yuan F, Wang Z. The human REV1 gene codes for a DNA template-dependent dCMP transferase. Nucleic Acids Res. 1999 Nov 15;27(22):4468-75. PMID:10536157
- ↑ Gibbs PE, Wang XD, Li Z, McManus TP, McGregor WG, Lawrence CW, Maher VM. The function of the human homolog of Saccharomyces cerevisiae REV1 is required for mutagenesis induced by UV light. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4186-91. PMID:10760286
- ↑ Masuda Y, Takahashi M, Tsunekuni N, Minami T, Sumii M, Miyagawa K, Kamiya K. Deoxycytidyl transferase activity of the human REV1 protein is closely associated with the conserved polymerase domain. J Biol Chem. 2001 May 4;276(18):15051-8. Epub 2001 Jan 22. PMID:11278384 doi:10.1074/jbc.M008082200
- ↑ Murakumo Y, Ogura Y, Ishii H, Numata S, Ichihara M, Croce CM, Fishel R, Takahashi M. Interactions in the error-prone postreplication repair proteins hREV1, hREV3, and hREV7. J Biol Chem. 2001 Sep 21;276(38):35644-51. Epub 2001 Aug 2. PMID:11485998 doi:10.1074/jbc.M102051200
- ↑ Kim H, Yang K, Dejsuphong D, D'Andrea AD. Regulation of Rev1 by the Fanconi anemia core complex. Nat Struct Mol Biol. 2012 Jan 22;19(2):164-70. doi: 10.1038/nsmb.2222. PMID:22266823 doi:10.1038/nsmb.2222
- ↑ Pozhidaeva A, Pustovalova Y, D'Souza S, Bezsonova I, Walker GC, Korzhnev DM. NMR Structure and Dynamics of the C-terminal Domain from Human Rev1 and its Complex with Rev1 Interacting Region of DNA Polymerase eta Biochemistry. 2012 Jun 13. PMID:22691049 doi:10.1021/bi300566z
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